The role of the innate immune response in HPV-related oral and oropharyngeal cancer

Introduction. During the last 20 years, the incidence of HPV-associated oropharyngeal cancer is increased. Principal actors of the innate immune response against HPV are represented by the TLRs (Toll like receptors). On the other hand different studies have reported that HPV can directly inhibit the functions of the TLRs pathway through interferons (IFNs). There are very few preliminary studies on the role of TLRs mediated HPV clearance in human oncology. Our study aim has been to evaluate whether TLR4 identifies HR-HPV integration state in OSCC. Methods. Protein levels of TLR4 in OSCC were assessed using Immunohistochemistry (IHC). In situ hybridization (ISH) for HPV-DNA detection in morphological context and Pyro-sequencing method have been performed in order to detect viral integration or episomic status. The relationship between TLR expression with or without HPV infection has been elucidated. Results. ISH HPV positive samples have reported lower TLR4 intensity than negative samples and it has confirmed by statistically significant difference (p = .002). There is no statistical correlation between TLR4 intensity and PCR HPV results (p > 0.05). Point-biserial correlation coefficient revealed statistically significant association between TLR4 expression and HR-HPV integration status (p = .0001) and between TLR4 expression index and HR-HPV infection (p = .001). Conclusions. We retain that TLR4 down-regulation is not associated to the histological tumoral grade but rather to HPV-16 infection and to its integration state into the host DNA.